The mitochondrial transporter SLC25A25 links ciliary TRPP2 signaling and cellular metabolism.
Public Library of Science (PLoS)
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Hofherr, A., Seger, C., Fitzpatrick, F., Busch, T., Michel, E., Luan, J., Osterried, L., et al. (2018). The mitochondrial transporter SLC25A25 links ciliary TRPP2 signaling and cellular metabolism.. PLoS biology, 16 (8), e2005651. https://doi.org/10.1371/journal.pbio.2005651
Cilia are organelles specialized in movement and signal transduction. The ciliary transient receptor potential ion channel polycystin-2 (TRPP2) controls elementary cilia-mediated physiological functions ranging from male fertility and kidney development to left-right patterning. However, the molecular components translating TRPP2 channel-mediated Ca2+ signals into respective physiological functions are unknown. Here we show that the Ca2+-regulated mitochondrial ATP-Mg/Pi carrier SLC25A25 acts downstream of TRPP2 in an evolutionarily conserved metabolic signaling pathway. We identify SLC25A25 as an essential component in this cilia-dependent pathway using a genome-wide forward genetic screen in Drosophila melanogaster, followed by a targeted analysis of SLC25A25 function in zebrafish left-right patterning. Our data suggest that TRPP2 ion channels regulate mitochondrial SLC25A25 transporters via Ca2+ establishing an evolutionarily conserved molecular link between ciliary signaling and mitochondrial metabolism.
Cilia, Animals, Zebrafish, Humans, Drosophila melanogaster, Calcium, Calcium-Binding Proteins, Amino Acid Transport Systems, Acidic, Ion Channels, Calcium Channels, Antiporters, Mitochondrial Membrane Transport Proteins, Mitochondrial Proteins, Signal Transduction, Heterozygote, TRPP Cation Channels
External DOI: https://doi.org/10.1371/journal.pbio.2005651
This record's URL: https://www.repository.cam.ac.uk/handle/1810/284892
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/